Phospholipase C-related but catalytically inactive protein is required for insulin-induced cell surface expression of γ-aminobutyric acid type A receptors

Makoto Fujii, Takashi Kanematsu, Hitoshi Ishibashi, Kiyoko Fukami, Tadaomi Takenawa, Keiichi I. Nakayama, Stephen J. Moss, Junichi Nabekura, Masato Hirata

研究成果: ジャーナルへの寄稿記事

40 引用 (Scopus)

抄録

The γ-aminobutyric acid type A (GABAA) receptors play a pivotal role in fast synaptic inhibition in the central nervous system. One of the key factors for determining synaptic strength is the number of receptors on the postsynaptic membrane, which is maintained by the balance between cell surface insertion and endocytosis of the receptors. In this study, we investigated whether phospholipase C-related but catalytically inactive protein (PRIP) is involved in insulin-induced GABAA receptor insertion. Insulin potentiated the GABA-induced Cl- current (IGABA) by about 30% in wild-type neurons, but not in PRIP1 and PRIP2 double-knock-out (DKO) neurons, suggesting that PRIP is involved in insulin-induced potentiation. The phosphorylation level of the GABAA receptor β-subunit was increased by about 30% in the wild-type neurons but not in the mutant neurons, which were similar to the changes observed in IGABA. We also revealed that PRIP recruited active Akt to the GABAA receptors by forming a ternary complex under insulin stimulation. The disruption of the binding between PRIP and the GABAA receptor β-subunit by PRIP interference peptide attenuated the insulin potentiation of IGABA. Taken together, these results suggest that PRIP is involved in insulin-induced GABAA receptor insertion by recruiting active Akt to the receptor complex.

元の言語英語
ページ(範囲)4837-4846
ページ数10
ジャーナルJournal of Biological Chemistry
285
発行部数7
DOI
出版物ステータス出版済み - 2 12 2010

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Aminobutyrates
Type C Phospholipases
GABA-A Receptors
Insulin
Neurons
Proteins
Phosphorylation
Induced currents
Neurology
Endocytosis
gamma-Aminobutyric Acid
Central Nervous System
Membranes
Peptides

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

これを引用

Phospholipase C-related but catalytically inactive protein is required for insulin-induced cell surface expression of γ-aminobutyric acid type A receptors. / Fujii, Makoto; Kanematsu, Takashi; Ishibashi, Hitoshi; Fukami, Kiyoko; Takenawa, Tadaomi; Nakayama, Keiichi I.; Moss, Stephen J.; Nabekura, Junichi; Hirata, Masato.

:: Journal of Biological Chemistry, 巻 285, 番号 7, 12.02.2010, p. 4837-4846.

研究成果: ジャーナルへの寄稿記事

Fujii, Makoto ; Kanematsu, Takashi ; Ishibashi, Hitoshi ; Fukami, Kiyoko ; Takenawa, Tadaomi ; Nakayama, Keiichi I. ; Moss, Stephen J. ; Nabekura, Junichi ; Hirata, Masato. / Phospholipase C-related but catalytically inactive protein is required for insulin-induced cell surface expression of γ-aminobutyric acid type A receptors. :: Journal of Biological Chemistry. 2010 ; 巻 285, 番号 7. pp. 4837-4846.
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